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Taking advantage of the highly permeable vasculature and lack of lymphatic drainage in solid tumors (EPR effect), nanosized drug delivery systems or nanomedicines have been extensively explored for tumor-targeted drug delivery. However, in most clinical cases tumors such as the early stage tumors and post-surgery microscopic residual tumors have not yet developed such pathological EPR features, i.e., EPR-deficient. Therefore, nanomedicines may not be applicable for such these tumors. Macrophages by nature can actively home and extravasate through the tight vascular wall into tumors and migrate to their hypoxic regions, and possess perfect stealth ability for long blood circulation and impressive phagocytosis for drug loadings. Thus, nanomedicines loaded in macrophages would harness both merits and gain the active tumor homing capability independent of the EPR effect for treatments of the EPR-deficient tumors. Herein, the critical considerations, current progress, challenges and future prospects of macrophages as carriers for nanomedicines are summarized, aiming at rational design of EPR-independent tumor-targeting active nanomedicines for targeted early and adjuvant cancer chemotherapy.

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Orally administrable anticancer nanomedicines are highly desirable due to their easy and repeatable administration, but are not yet feasible because the current nanomedicine cannot simultaneously overcome the strong mucus and villi barriers and thus have very low bioavailability (BA). Herein, this work presents the first polymeric micelle capable of fast mucus permeation and villi absorption and delivering paclitaxel (PTX) efficiently to tumors with therapeutic efficacy even better than intravenously administered polyethylene glycol based counterpart or free PTX. Poly[2‐(N‐oxide‐N,N‐diethylamino)ethyl methacrylate] (OPDEA), a water‐soluble polyzwitterion, is highly nonfouling to proteins and other biomacromolecules such as mucin but can weakly bind to phospholipids. Therefore, the micelle of its block copolymer with poly(ε‐caprolactone) (OPDEA‐PCL) can efficiently permeate through the viscous mucus and bind to villi, which triggers transcytosis‐mediated transepithelial transport into blood circulation for tumor accumulation. The orally administered micelles deliver PTX to tumors, efficiently inhibiting the growth of HepG2 and patient‐derived hepatocellular carcinoma xenografts and triple‐negative breast tumors. These results demonstrate that OPDEA‐based micelles may serve as an efficient oral nanomedicine for delivering other small molecules or even large molecules.

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Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

The cancer drug delivery process involves a series of biological barriers, which require the nanomedicine to exhibit different, even opposite properties for high therapeutic efficacy. The prevailing design philosophy, i.e., integrating these properties within one nanomedicine via on‐demand property transitions such as PEGylation/dePEGylation, complicates nanomedicines’ composition and thus impedes clinical translation. Here, polyzwitterionic micelles of poly(tertiary amine‐oxide)‐ block ‐poly( ε ‐caprolactone) (PTAO‐PCL) amphiphiles that enable all the required functions are presented. The zwitterionic nature and unique cell membrane affinity confer the PTAO micelles long blood circulation, efficient tumor accumulation and penetration, and fast cellular internalization. The mitochondrial targeting capability allows drug delivery into the mitochondria to induce mitochondrial dysfunction and overcome tumor multidrug resistance. As a result, the PTAO/drug micelles exhibit potent anticancer efficacy. This simple yet multipotent carrier system holds great promise as a generic platform for potential clinical translation.

Microelements such as copper are essential and involved in various biological processes and under strict homeostatic regulation. Compared to healthy individuals, cancer patients have aberrantly elevated intratumoral and systemic copper levels, which promote tumorigenesis, angiogenesis, tumor metastasis, and recurrence of diverse human cancers.